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Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease (NICE)

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ClinicalTrials.gov Identifier: NCT03743636
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : November 16, 2018
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Mary McDermott, Northwestern University

Tracking Information
First Submitted Date  ICMJE May 20, 2018
First Posted Date  ICMJE November 16, 2018
Last Update Posted Date November 16, 2018
Actual Study Start Date  ICMJE October 1, 2018
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • Six-minute walk distance (NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR alone improves six-minute walk distance at 6-month follow-up, compared to placebo.
  • Six-minute walk distance (NR/resveratrol vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR combined with resveratrol improves six-minute walk performance at 6-month follow-up, compared to placebo.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • Maximal treadmill walking time (NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR alone improves maximal treadmill walking time at 6-month follow-up, compared to placebo.
  • Walking Impairment Questionnaire (WIQ) distance score (NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR alone improves the WIQ distance score at 6-month follow-up, compared to placebo.
  • Maximal treadmill walking time (NR/resveratrol vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR combined with resveratrol improves maximal treadmill walking time at 6-month follow-up, compared to placebo.
  • Walking Impairment Questionnaire (WIQ) distance score (NR/resveratrol vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR combined with resveratrol improves the WIQ distance score at 6-month follow-up, compared to placebo.
  • Calf muscle changes (increased satellite cell abundance) [ Time Frame: Baseline to 6-month follow-up ]
    We will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone haveincreased satellite cell abundance compared to the placebo group.
  • Calf muscle changes (NAD+ abundance) [ Time Frame: Baseline to 6-month follow-up ]
    We will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have increased calf muscle NAD+ abundance, compared to the placebo group.
  • Calf muscle changes (improved muscle fiber phenotype) [ Time Frame: Baseline to 6-month follow-up ]
    We will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have improved muscle fiber phenotype, compared to the placebo group.
  • Six-minute walk distance (NR/Resveratrol or NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in six-minute walk distance, compared to those randomized to placebo.
  • Maximal treadmill walking time (NR/resveratrol or NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in maximal treadmill walking time, compared to those randomized to placebo.
  • Walking Impairment Questionnaire (WIQ) distance score (NR/resveratrol or NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in WIQ distance score, compared to those randomized to placebo.
  • Physical Activity (NR/resveratrol or NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in physical activity, compared to those randomized to placebo.
  • NAD+ Abundance (NR/resveratrol or NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in NAD+ abundance, compared to those randomized to placebo.
  • Satellite Cell Abundance (NR/resveratrol or NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in satellite cell abundance, compared to those randomized to placebo.
  • Muscle Fiber Phenotype(NR/resveratrol or NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in muscle fiber phenotype, compared to those randomized to placebo.
  • Physical activity (NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR alone improves physical activity at 6-month follow-up, compared to placebo.
  • Physical activity (NR/Resveratrol vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR combined with resveratrol improves physical activity at 6-month follow-up, compared to placebo.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 13, 2018)
  • Walking Impairment Questionnaire (WIQ) speed and stair climbing score (NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR alone improves the WIQ speed and stair climbing score at 6-month follow-up, compared to placebo.
  • Short-Form Physical Functioning (SF-36) score (NR alone vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR alone improves the WIQ speed and stair climbing scores and the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo.
  • Walking Impairment Questionnaire (WIQ) speed and stair climbing score (NR/resveratrol vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR combined with resveratrol improves the WIQ speed and stair climbing scores at 6-month follow-up, compared to placebo.
  • Short-Form Physical Functioning (SF-36) score (NR/resveratrol vs. placebo) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR combined with resveratrol improves the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo.
  • Six-minute walk (NR/resveratrol vs. NR alone) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether those randomized to NR + resveratrol have greater improvement in the six-minute walk compared to those randomized to NR alone.
  • Maximal treadmill walking time (NR/resveratrol vs. NR alone) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether those randomized to NR + resveratrol have greater improvement in maximal treadmill walking time compared to those randomized to NR alone.
  • Walking Impairment Questionnaire (WIQ) distance score (NR/resveratrol vs. NR alone) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether those randomized to NR + resveratrol have greater improvement in the WIQ distance score compared to those randomized to NR alone.
  • Physical activity (NR/Resveratrol vs. NR alone) [ Time Frame: Baseline to 6-month follow-up ]
    Among participants with PAD, we will determine whether NR/reseveratrol improves physical activity at 6-month follow-up, compared to NR alone.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease
Official Title  ICMJE Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease: The NICE Trial
Brief Summary

NICE is a randomized clinical trial that will examine the effects of nicotinamide riboside (NR) both with and without resveratrol to test whether, among people with PAD, NR significantly improves walking performance more than placebo and whether NR combined with resveratrol significantly improves walking performance more than placebo. If our findings support our hypotheses, results will be used to design a large, definitive randomized clinical.

We will randomize 90 participants with PAD to one of the following three groups: NR + resveratrol, NR + placebo, or placebo + placebo. Our primary outcome is change in six-minute walk distance between baseline and 6-month follow-up. Secondary outcomes are change in maximal treadmill walking time, patient-reported walking ability (measured by the Walking Impairment Questionnaire (WIQ)), quality of life (measured by the Short Form-36 Physical Functioning (SF-36 PF) score), and physical activity (measured by accelerometer). Calf skeletal muscle biopsy specimens collected in participants in the NICE Trial will be analyzed for NAD+ abundance, stem cell (satellite cell) abundance and muscle fiber phenotype.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Peripheral Artery Disease
Intervention  ICMJE
  • Drug: Nicotinamide riboside
    Participants randomized to the NR + resveratrol arm or the NR + placebo arm of the study will receive 1,000 mg of NR daily for six months.
    Other Names:
    • NR
    • Niagen
  • Drug: Resveratrol
    Participants randomized to the NR + resveratrol arm of the study will receive 125 mg of resveratrol daily for six months.
  • Other: Placebo
    Participants randomized to the NR + placebo arm of the study will receiving placebo pills that are identical in appearance to resveratrol. Participants randomized to the placebo + placebo arm of the study will receive pills that are identical in appearance to NR and resveratrol. Participants will receive placebo pills daily for six months.
Study Arms  ICMJE
  • Active Comparator: Nicotinamide riboside + resveratrol
    Participants randomized to the NR + resveratrol arm of the study will receive 1,000 mg of NR and 125 mg of reservatrol daily for six months.
    Interventions:
    • Drug: Nicotinamide riboside
    • Drug: Resveratrol
  • Active Comparator: Nicotinamide riboside + placebo
    Participants randomized to the NR + placebo arm of the study will receive 1,000 mg of NR and a placebo daily for six months.
    Interventions:
    • Drug: Nicotinamide riboside
    • Other: Placebo
  • Placebo Comparator: Placebo + placebo
    Participants randomized to the placebo + placebo arm of study will receive placebo pills.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 13, 2018)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

All participants will have PAD. PAD will be defined as an ankle-brachial index (ABI) <0.90 at the baseline study visit.

Exclusion Criteria:

  1. Above- or below-knee amputation.
  2. Critical limb ischemia.
  3. Wheelchair-bound or requiring a walker to ambulate.
  4. Walking is limited by a symptom other than PAD.
  5. Current foot ulcer on bottom of foot.
  6. End stage renal disease defined as a GFR less than 20 ml/min/1.73 M2.
  7. Significant liver impairment defined as two or more hepatic function enzymes >3.0 times the upper limit of normal. [NOTE: participants who meet this criterion may undergo a re-test of hepatic function tests to determine whether initially elevated hepatic enzymes represented a transient or spurious phenomenon.]
  8. Failure to successfully complete the 2-week study run-in.
  9. Planned lower extremity revascularization, orthopedic surgery, or other major surgery during the next six months.
  10. Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary revascularization, or other major surgery in the previous three months.
  11. Participation in supervised treadmill exercise during the previous three months.
  12. Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. [NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.]
  13. Mini-Mental Status Examination (MMSE) score <23 or dementia.
  14. Participation in or completion of a clinical trial in the previous three months. [NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.]
  15. Currently taking study drug(s) or has taken study drug(s) in past six months.
  16. Increase in angina or angina at rest
  17. Non-English speaking.
  18. Visual impairment that limits walking ability.
  19. Women who are pregnant or who are pre-menopausal will not be eligible.
  20. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.

Potentially eligible participants will be advised that Medicare coverage for 12 weeks of supervised treadmill exercise is now available. Potential participants who have not participated in supervised treadmill exercise covered by Medicare and who desire to participate will be referred back to their physician for follow-up. These individuals may become eligible six months after they complete supervised treadmill exercise.

Vulnerable populations (fetuses, pregnant women, children, prisoners, and institutionalized persons) and adults unable to consent will not be included in the study.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mary M McDermott, MD 312-503-6419 mdm608@northwestern.edu
Contact: Kathryn Domanchuk, BS 3125036438 k-domanchuk@northwestern.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03743636
Other Study ID Numbers  ICMJE STU00206660
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mary McDermott, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE American Heart Association
Investigators  ICMJE
Principal Investigator: Mary M McDermott, MD Northwestern University
PRS Account Northwestern University
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP